A newly proposed draft guidance on the development of regenerative medicine therapies has prompted significant feedback from industry groups, research organizations, and professional associations. While stakeholders broadly support efforts to strengthen pathways for advanced therapies, many are asking for greater clarity on eligibility criteria for the Regenerative Medicine Advanced Therapy (RMAT) designation and how it should be applied in practice.
Questions About What Qualifies for RMAT
One of the most common concerns raised in comments relates to which products fall under the scope of the updated guidance. The Pharmaceutical Research and Manufacturers of America (PhRMA) urged regulators to clarify whether human gene therapies or genetically modified cellular therapies meet the definition of a regenerative medicine therapy. Stakeholders noted that ambiguous language around exclusions could create confusion for sponsors planning early development strategies.
PhRMA also asked for clearer expectations around developing and validating critical quality attributes (CQAs), emphasizing that CQA development for regenerative products is often iterative. The group suggested allowing sponsors to draw on data from related products or analytical platforms to support early CQA development.
Flexibility in Clinical Trial Design
Several organizations, including the Association of Clinical Research Organizations (ACRO), supported the inclusion of alternative trial designs and external controls—particularly for small patient populations where randomized studies may not be feasible. However, ACRO noted that the draft guidance introduces uncertainty around the requirement for data from a “meaningful number of study sites.” For ultra-rare conditions, sponsors warned that such a requirement could limit pathway eligibility unless clarified.
Stakeholders also encouraged clearer examples of preliminary clinical evidence, details on when RMAT requests may be denied, and scenarios where the designation could be rescinded. Many expressed a desire for more transparency around how regulatory decisions are made and how sponsors can proactively address potential gaps.
Understanding When RMAT Status May Be Withdrawn
Because the draft guidance allows regulators to rescind RMAT designation if a therapy no longer meets qualifying criteria, commenters asked for more explicit explanations. Suggested additions included:
• Examples of conditions under which RMAT status may be withdrawn
• Whether the designation can be reinstated after mitigation
• Recommended planning steps to reduce the risk of losing eligibility
Stakeholders noted that clearer expectations would help sponsors manage development timelines and regulatory strategy more effectively.
Early Engagement and Alignment
The Alliance for Regenerative Medicine recommended reinstating explicit reference to INTERACT meetings for early interaction with the Center for Biologics Evaluation and Research (CBER). Stakeholders stressed that early alignment on quality, endpoints, and development strategy is critical for programs pursuing expedited pathways.
Others, including the Institute for Gene Therapies, emphasized the need for consistent expectations on manufacturing comparability, the use of surrogate or intermediate endpoints, and real-world evidence in confirmatory studies. They cautioned that inconsistent approaches could slow innovation rather than accelerate it.
Looking Ahead
The updated guidance aims to provide a clearer regulatory roadmap for regenerative medicine therapies addressing serious or life-threatening conditions. However, commenters have made it clear that additional detail is needed to support predictable development pathways and ensure sponsors can make full use of RMAT and other expedited programs.
As regulators refine the guidance, ongoing dialogue with sponsors and patient groups will remain essential to balancing scientific rigor with development flexibility.
At EMMA International
EMMA International supports developers of regenerative medicine and advanced therapy products through every stage of the regulatory lifecycle. Our experts assist with:
• RMAT, Breakthrough, and Fast Track submission strategies
• Clinical and CMC readiness for expedited programs
• Quality and CQA framework development
• Regulatory meeting preparation and documentation
We ensure your program remains aligned with evolving expectations while maintaining compliance, scientific integrity, and patient safety.
For more information on how EMMA International can assist, visit www.emmainternational.com or contact us at (248) 987-4497 or info@emmainternational.com.
Reference:
Craven, J. (2025, December 1). Commenters seek details on RMAT designation. Regulatory Affairs Professionals Society.
U.S. Food and Drug Administration. (2025). Draft guidance for regenerative medicine therapies: Development and considerations.
